{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:04:18Z","timestamp":1784221458800,"version":"3.55.0"},"posted":{"date-parts":[[2025,1,12]]},"group-title":"Urology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T00:00:00Z","timestamp":1736640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Younger patients with bladder cancer typically have fewer environmental exposures or risk factors, suggesting that the molecular pathways implicated in early-onset disease differ from those in older patients. Dissecting the genomic profiles of early-onset tumors may inform targeted treatment strategies for young patients. We compared the frequency of somatic mutations in early-onset bladder cancer, defined as a diagnosis before the age of 55 years, which encompasses the youngest patients in about 1 in 10 diagnoses based on national registries.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Material and methods<\/jats:title>\n                  <jats:p>We assessed two institutional cohorts: the Mass General Brigham Young Cystectomy Cohort (MGB-YCC, n=134 patients) from 2008-2023 and the Memorial Sloan-Kettering-IMPACT bladder cancer cohort (MSK-IMPACT, n=1271 including n=207 cystectomy and n=811 transurethral resection (TUR) specimens from 2014-2021. Clinical outcomes of MGB-YCC were also compared with published data from patients undergoing cystectomy in the National Surgical Quality Improvement Program (NSQIP, n=10,848) from 2008-2013.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Both the MGB-YCC and MSK-IMPACT cohorts were predominantly male (&gt;75%), and younger patients had lower rates of smoking history or muscle-invasive disease. MGB-YCC demonstrated more patients with continent diversions (51.5% vs 14.9%) than the older population in NSQIP, although complication rates were similar. Genomic characterization of MGB-YCC demonstrated enrichment in younger patients of TP53 (65% overall, 83% &lt;50-year-old, p=0.045) and\n                    <jats:italic>KMT2D<\/jats:italic>\n                    mutations almost exclusively in the youngest patients (35% overall, 83% &lt;45-years-old, p=0.008). MSK-IMPACT revealed a significant increase in\n                    <jats:italic>FGFR3<\/jats:italic>\n                    mutations in younger patients in both cystectomy (33% vs 13%, p=0.014) and TUR (45% vs 27%, p&lt;0.001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results indicate that early-onset bladder cancer is a distinct patient population that has disease driven by specific somatic mutations, some of which represent therapeutic targets. This suggests potential benefits of genomic tumor profiling in guiding personalized treatment.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.10.25320337","type":"posted-content","created":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T14:25:19Z","timestamp":1736691919000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical and genomic profiling of early-onset bladder cancer identifies key alterations and therapeutic targets"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-9832","authenticated-orcid":false,"given":"Christopher J.","family":"Magnani","sequence":"first","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent D.","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"},{"name":"Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Garcia","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Urology, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ernandez","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendrick","family":"Yim","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Kibel","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mossanen","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Preston","sequence":"additional","affiliation":[{"name":"Department of Urology, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard H.","family":"Bochner","sequence":"additional","affiliation":[{"name":"Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Solit","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene J.","family":"Pietzak","sequence":"additional","affiliation":[{"name":"Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent W.","family":"Mouw","sequence":"additional","affiliation":[{"name":"Department of Radiation 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